Project Summary/Abstract Chronic obstructive pulmonary disease (COPD) has risen to the third leading cause of death in the US and specific and effective therapies are not available. Age is the most important risk factor for COPD. The mechanisms of age-related changes that lead to COPD pathogenesis are poorly understood. In this proposal, we will study whether Miz1 epigenetically represses NF-?B-dependent components of senescence-associated secretory phenotype (SASP), which acts in cooperation with inhibition of cell cycle arrest to suppress the senescence program, thereby preventing the development of COPD. Completion of this proposal, which includes animal and human studies, will provide fundamental insights into the pathogenesis of COPD and thus provide therapeutic targets.